This project concerns the study of the autologous mixed lymphocyte reaction (AMLR), the proliferative response of T cells induced by exposure to autologous B cells or macrophages. In previous studies we have shown that 1) the AMLR is reduced in primary biliary cirrhosis (PBC), an autoimmune disease characterized by chronic hepatic inflammation and biliary obstruction; 2) the AMLR results mainly in the proliferation of T cells which can suppress pokeweed mitogen-driven Ig synthesis in vitro; 3) the AMLR is augmented tenfold if the stimulating autologous cells (B cells) are pre-activated with EB virus or non-specific mitogens. These and other data suggest that the immunoregulatory abnormality found in PBC (in other autoimmune diseases) is due to the failure to generate suppressor T cells via the AMLR. To define further the T cells which react in the autologous MLR we have now established long term autoreactive T cell lines and have begun to define the function properties of cells in such lines. These autoreactive T cell lines were generated by repeated stimulation of T cells with autologous non-T cells (B cells and macrophages), in the presence of IL-2. The cells populations obtained respond to autologous cells but not to allogeneic cells; in addition, they do not respond to various mitogens or antigens. In initial studies we have focused on the cytotoxic capability of the autoreactive T cell lines. We have found that the Leu2-positive subpopulation (comprising 80% of the cell line) contained NK-like cytotoxicity although the cells in this subpopulation lacked markers usually associated with NK cells. In addition, we have found the Leu 2-positive sub-population (comprising 20% of the cell line) contained cells capable of killing autologous B cells (both activated and unactivated B cells). These studies indicate that the AMLR, contrary to previous findings, does result in the generation of cells capable of self-killing. Furthermore, they show that autoreactive lines contain cells capable of mediating NK cytotoxicity, but this is probably due to direct stimulation of NK cells by IL-2 present in the medium.